We are studying the ets family oftranscription factors and their possible role inhuman malignancies. The focus of our work in thepast few years has been the ERF gene, a newets-domain protein that we identified inthis Laboratory. ERF is a potenttranscriptional repressor that can act as atumor-suppressor gene in certain in vitrosystems (ras-transformed NIH3T3 cells). Theactivity of ERF is regulated by the Erk kinaseswhich can associate and phosphorylate the proteinin vivo and in vitro. Data from ourlab and that of our collaborators (G. Rubin, UCSF;M. McMahon, DNAX) indicate that ERF is an effectorprotein in the RAS/RAF signaling pathway. Ourcurrent efforts are aiming to determine thefunction of ERF, the mechanism of itsregulation, and its possible association withhuman malignancies. To that extent we analyzed itsphysical association with other proteins by theyeast two-hybrid system and GST-fusion protein"pull down", and its subcellulartrafficking by immuno- fluorescence in the contextof its phosphorylation. We are also in the processof generating a KO mouse and looking into humanpathologies associated with chr19q13.1- 13.2 wherethe ERF gene is localized.